No abstract

We report our experience with oral busulfan (BU) in 159 consecutive patients to evaluate the safety of home administration. Patients received a myeloablative BUcontaining regimen, including oral anticonvulsant and antiemetic prophylaxis, followed by hematopoietic stem cell transplantation. Comprehensive verbal and written education was provided. Pharmacokinetic monitoring was performed and dose adjustments were made to target an area under the plasma concentration-time curve (AUC) of 900-1500 lmol.min/l. Safety was assessed by evaluating therapy-related toxicities, including seizures, venoocclusive disease (VOD) and patient tolerability. The utilization of pharmacokinetic monitoring was reviewed as a secondary end point. Of the 143 patients evaluated for BU-related seizures and VOD, only two (1.4%) experienced a generalized seizure and four patients (3%) were diagnosed with VOD. VOD resolved in three patients and was a contributing cause of death in one patient. Additional BU dosing owing to nausea and/or vomiting occurred in 28 patients (18%) and five patients (3%) were hospitalized. The median measured AUC was 1405 lmol. min/l, 68% of patients required a dose adjustment, and the median total administered BU dose was 13.6 mg/kg. In conclusion, high-dose oral BU can be safely administered on an outpatient basis.

No abstract

Myeloablative allogeneic stem cell transplantation (allo-SCT) is accompanied by a high risk of transplant related toxicity (TRT), traditionally requiring recipients to stay hospitalized until recovery from the cytopenic phase. The median hospital stay for allo-SCT in most institutions ranges from 25 to 30 days. We developed a comprehensive outpatient approach to the management of patients undergoing myeloablative allo-SCT. Although potential benefits include decreased hospital utilization/costs and increased patient satisfaction, there is little data regarding its feasibility and safety. We reviewed the clinical outcomes of 100 consecutive matched-related donor (MRD) myeloablative allo-SCT recipients transplanted at a single institution between March 2000 and February 2006. Excluding the planned admission for stem cell infusion on Day 0, all other aspects of their management (myeloablative conditioning, supportive care) were to be performed outpatient. Expectant admission occurred for complications more safely managed in the hospital (febrile neutropenia, decreased oral intake, uncontrolled pain, etc.). Exceptions to this model occurred for patients with circumstances that might compromise the safety of outpatient management, otherwise this was standard practice. One hundred consecutive transplant recipients (median age of 44 years [range 21–64]), underwent MRD myeloablative allo-SCT for high risk (58%) or standard risk (42%) hematologic malignancies, receiving either high-dose busulfan- (81%) or TBI- (19%) based preparative regimens. Peripheral blood was the stem cell source for 89 patients, bone marrow for 10, and one received a mixed graft. Only thirteen patients required hospital admission to receive at least a portion of their preparative regimen for reasons of compliance/communication barriers (4), GI toxicity (3), fever (1), or medical condition(5). Sixty patients were stable for hospital discharge either the day of or day after stem cell infusion. The median time from stem cell infusion to the first readmission was Day +7 (range 3–69). The median hospital length of stay (LOS) from the start of the preparative regimen through Day +30 was 12 days (range 1–44 days). The median 100 day LOS was 15 days (range 1–66). Median times to neutrophil and platelet engraftment were 12 and 19 days, respectively. Neutropenic fever occurred in 45 patients and was the primary cause for hospital readmission. Early suspected invasive fungal infections (before Day +30) occurred in 10 patients. CMV reactivation before Day +100 occurred in 28 patients. Acute (grade II-IV) and chronic graft versus host disease occurred in 34% and 56% of patients, respectively. Rates of 100 day and 6 month non-relapse mortality were 10% and 16%, respectively. With a median follow-up of 3.6 years (range 0.5–6.5), the estimated 5 year disease-free and overall survival (OS) were 49% and 51%, respectively. Stratifying for disease risk, OS in patients with standard versus high risk disease was 64% and 41%, respectively. In summary, outpatient myeloablative allo-SCT with expectant inpatient management for TRT can be done safely with transplant outcomes comparable to those reported in the literature for conventional allo-SCT. This approach significantly decreases the length of inpatient hospitalization for allo-SCT, with the potential to free up inpatient resources, improve quality of life, and decrease costs.